Bronchoscopy in the emergency department.

BACKGROUND: Flexible bronchoscopy has been safely used for decades in ambulatory and critical care settings to aid in the diagnosis and treatment of tracheobronchial tree disorders. Although emergency physicians have the requisite skills to operate and interpret flexible bronchoscopy, no reports exist on the use of bronchoscopy by emergency physicians apart from endotracheal tube placement and confirmation. OBJECTIVE: The primary goal of this study was to describe the indications, outcomes and complications of flexible bronchoscopy performed by emergency physicians in an urban academic emergency department. METHODS: This was a single-center retrospective cohort study involving chart and video review of 146 patients over a 10.5-year study period. Patients of any age were included if they had been tracheally intubated or mechanically ventilated and underwent flexible bronchoscopy in the emergency department. After patients were identified, manual chart and video review was used to collect data on patient demographics, indications for intubation, indications for bronchoscopy, details of the bronchoscopy procedure, procedural findings, outcomes of the procedure, complications, provider training levels, and additional bronchoscopies performed after admission. The data was analyzed using descriptive statistics. RESULTS: 146 patients were included in the study and all bronchoscopies were performed or supervised by attending emergency physicians. After bronchoscopy, 24% of patients displayed improvement in oxygenation or lobar collapse while most patients had no change in clinical status. One patient had temporary hypoxemia after bronchoscopy. When another physician performed a subsequent bronchoscopy during admission, the findings were in agreement with the ED bronchoscopy 86% of the time. CONCLUSION: At our institution, emergency physicians can safely and effectively use flexible bronchoscopy to diagnose and treat critically ill patients.

THE HENNEPIN DOUBLE-TUBE TECHNIQUE: A MORE EFFICIENT METHOD OF TRACHEAL INTUBATION THROUGH THE LMA FASTRACH.

BACKGROUND: The LMA Fastrach (LMA North America, Inc; hereafter termed the intubating laryngeal mask airway [ILMA]) is an extraglottic device designed to facilitate endotracheal intubation. After the endotracheal tube is placed through the lumen of the ILMA into the trachea, the ILMA is removed, using a proprietary stabilizer rod to hold the tube in place. DISCUSSION: The traditional method of ILMA removal is not optimized for the critically ill patient. It requires the use of unfamiliar equipment, exposes the patient to a significant period without ventilation, and risks tube dislodgement. We designed a simple technique with a double-endotracheal tube setup that addresses these problems using common equipment, allowing for continuous ventilation, and minimizing the risk of tube dislodgement. CONCLUSIONS: The traditional method of ILMA removal around an endotracheal tube is not designed for critically ill patients or the physicians taking care of them. This novel technique is designed to improve the usability of the ILMA for physicians and improve airway outcomes for patients.

Rapid Sequence Airway with the Intubating Laryngeal Mask in the Emergency Department.

BACKGROUND: The administration of sedation and neuromuscular blockade to facilitate extraglottic device (EGD) placement is known as rapid sequence airway (RSA). In the emergency department (ED), EGDs are used largely as rescue devices. In select patients, there may be significant advantages to using EGDs over laryngoscopy as the primary airway device in the ED. OBJECTIVE: Our study sought to describe the practice of RSA in the ED, including rates of successful oxygenation, ventilation, and complications from EGD use. METHODS: We identified patients in the ED between 2007 and 2017 who underwent RSA with the LMA® Fastrach™ (hereafter termed ILMA; Teleflex Medical Europe Ltd., Athlone, Ireland) placed as the first definitive airway management device. A trained abstractor performed chart and video review of the cases to determine patient characteristics, physician use of the ILMA, indication for ILMA placement, success of oxygenation and ventilation, success of intubation, and complications related to the device. RESULTS: During the study period, 94 patients underwent RSA with the ILMA. Of those, 93 (99%) were successfully oxygenated and ventilated, and when intubation was attempted, 89% were able to be intubated through the ILMA. The incidence of vomiting and aspiration was 1% and 3%, respectively. There were 30 different attending physicians who supervised RSA and the median number was 2 per physician in the 10-year study period. CONCLUSION: The practice of RSA with the ILMA in the ED is associated with a high rate of successful oxygenation, ventilation, and intubation with infrequent complications, even when performed by physicians with few experiences in the approach.

Reading What the Mind Thinks From How the Eye Sees.

Human eyes convey a remarkable variety of complex social and emotional information. However, it is unknown which physical eye features convey mental states and how that came about. In the current experiments, we tested the hypothesis that the receiver's perception of mental states is grounded in expressive eye appearance that serves an optical function for the sender. Specifically, opposing features of eye widening versus eye narrowing that regulate sensitivity versus discrimination not only conveyed their associated basic emotions (e.g., fear vs. disgust, respectively) but also conveyed opposing clusters of complex mental states that communicate sensitivity versus discrimination (e.g., awe vs. suspicion). This sensitivity-discrimination dimension accounted for the majority of variance in perceived mental states (61.7%). Further, these eye features remained diagnostic of these complex mental states even in the context of competing information from the lower face. These results demonstrate that how humans read complex mental states may be derived from a basic optical principle of how people see.

The Face of Distaste: A Preliminary Study.

Distaste is a primitive rejection impulse triggered by the ingestion of unpleasant tasting substances, many of which are toxic. Theoretical work has suggested that distaste may be the evolutionary precursor for both physical disgust, which serves to defend against disease and other threats to biological fitness, and moral disgust, which defends against threats to the social order. Consistent with this proposal, recent work has found that the facial expression of distaste may be similar to that of disgust. Specifically, raising of the upper lip has been reported in distaste, physical disgust, and moral disgust. However, competing evidence suggests that distaste and disgust expressions may differ, and the facial expressions of adult humans in response to distasteful stimuli remain poorly specified. To address this issue, we conducted a preliminary experiment to investigate the upper lip raise in adult volunteers (N = 15) as they tasted unpleasant, pleasant, and neutral liquids. We found increased raising of the upper lip for bitter and salty tastes relative to water and sweet, suggesting that the upper lip raise is indeed part of the distaste expression. Given evidence that the upper lip raise is also present in physical and moral disgust, these results are consistent with the proposed origins of disgust in distaste.

Terminal QRS distortion is present in anterior myocardial infarction but absent in early repolarization.

BACKGROUND: Early repolarization (ER) and acute left anterior descending artery occlusion (LADO) may be difficult to distinguish. Terminal QRS distortion (TQRSD), defined by the absence of both an S wave and J wave in either of leads V2 or V3, is often present in anterior ST-segment elevation myocardial infarction. We hypothesized that this finding would always be absent in ER. METHODS: This was a retrospective analysis of electrocardiograms (ECGs) of consecutive patients who presented to the emergency department with ischemic symptoms and had a cardiologist interpretation of "benign ER" on the initial emergency department ECG. All ECGs were scrutinized for the presence of an S wave and a J wave in leads V2 and V3. Differences in S-wave amplitudes between complexes with and without J waves were analyzed using nonparametric Mann-Whitney testing and confidence intervals around a proportion. RESULTS: One hundred seventy-one patients were identified with benign ER. Zero of 171 had TQRSD (specificity for LADO, 100%; 95% confidence interval, 97.8-100). In lead V2, S waves were absent in only 1 of 171 ECGs; however, in that ECG, a J wave measuring 0.5 mm was present. In lead V3, S waves were absent in 16 ECGs, but all of these ECGs had J waves. When J waves were absent in leads V2 or V3, the corresponding S waves were deeper than S waves in QRS complexes with J waves. CONCLUSION: Terminal QRS distortion was never observed in benign ER. Based on previous studies indicating the presence of TQRSD in LADO, it was, thus, 100% specific to LADO when the differential diagnosis was acute myocardial infarction vs ER.

Optical origins of opposing facial expression actions.

Darwin theorized that emotional expressions originated as opposing functional adaptations for the expresser, not as distinct categories of social signals. Given that two thirds of the eye's refractive power comes from the cornea, we examined whether opposing expressive behaviors that widen the eyes (e.g., fear) or narrow the eyes (e.g., disgust) may have served as an optical trade-off, enhancing either sensitivity or acuity, thereby promoting stimulus localization ("where") or stimulus discrimination ("what"), respectively. An optical model based on eye apertures of posed fear and disgust expressions supported this functional trade-off. We then tested the model using standardized optometric measures of sensitivity and acuity. We demonstrated that eye widening enhanced stimulus detection, whereas eye narrowing enhanced discrimination, each at the expense of the other. Opposing expressive actions around the eye may thus reflect origins in an optical principle, shaping visual encoding at its earliest stage-how light is cast onto the retina.

Highly multiplexed design of an allosteric transcription factor to sense novel ligands.

Allosteric transcription factors (aTF), widely used as biosensors, have proven challenging to design for detecting novel molecules because mutation of ligand-binding residues often disrupts allostery. We developed Sensor-seq, a high-throughput platform to design and identify aTF biosensors that bind to non-native ligands. We screened a library of 17,737 variants of the aTF TtgR, a regulator of a multidrug exporter, against six non-native ligands of diverse chemical structures - four derivatives of the cancer therapeutic tamoxifen, the antimalarial drug quinine, and the opiate analog naltrexone - as well as two native flavonoid ligands, naringenin and phloretin. Sensor-seq identified novel biosensors for each of these ligands with high dynamic range and diverse specificity profiles. The structure of a naltrexone-bound design showed shape-complementary methionine-aromatic interactions driving ligand specificity. To demonstrate practical utility, we developed cell-free detection systems for naltrexone and quinine. Sensor-seq enables rapid, scalable design of new biosensors, overcoming constraints of natural biosensors.

Characterization of nucleosome positioning in hepadnaviral covalently closed circular DNA minichromosomes.

Hepadnaviral covalently closed circular DNA (cccDNA) exists as an episomal minichromosome in the nucleus of virus-infected hepatocytes, and serves as the transcriptional template for the synthesis of viral mRNAs. To obtain insight on the structure of hepadnaviral cccDNA minichromosomes, we utilized ducks infected with the duck hepatitis B virus (DHBV) as a model and determined the in vivo nucleosome distribution pattern on viral cccDNA by the micrococcal nuclease (MNase) mapping and genome-wide PCR amplification of isolated mononucleosomal DHBV DNA. Several nucleosome-protected sites in a region of the DHBV genome [nucleotides (nt) 2000 to 2700], known to harbor various cis transcription regulatory elements, were consistently identified in all DHBV-positive liver samples. In addition, we observed other nucleosome protection sites in DHBV minichromosomes that may vary among individual ducks, but the pattern of MNase mapping in those regions is transmittable from the adult ducks to the newly infected ducklings. These results imply that the nucleosomes along viral cccDNA in the minichromosomes are not random but sequence-specifically positioned. Furthermore, we showed in ducklings that a significant portion of cccDNA possesses a few negative superhelical turns, suggesting the presence of intermediates of viral minichromosomes assembled in the liver, where dynamic hepatocyte growth and cccDNA formation occur. This study supplies the initial framework for the understanding of the overall complete structure of hepadnaviral cccDNA minichromosomes.

Social transmission of the sensory benefits of eye widening in fear expressions.

Facial expressions may have originated from a primitive sensory regulatory function that was then co-opted and further shaped for the purposes of social utility. In the research reported here, we tested such a hypothesis by investigating the functional origins of fear expressions for both the expresser and the observer. We first found that fear-based eye widening enhanced target discrimination in the available visual periphery of the expresser by 9.4%. We then found that fear-based eye widening enhanced observers' discrimination of expressers' gaze direction and facilitated observers' responses when locating eccentric targets. We present evidence that this benefit was driven by neither the perceived emotion nor attention but, rather, by an enhanced physical signal originating from greater exposure of the iris and sclera. These results highlight the coevolution of sensory and social regulatory functions of emotional expressions by showing that eye widening serves to enhance processing of important environmental events in the visual fields of both expresser and observer.

Genes for emotion-enhanced remembering are linked to enhanced perceiving.

Emotionally enhanced memory and susceptibility to intrusive memories after trauma have been linked to a deletion variant (i.e., a form of a gene in which certain amino acids are missing) of ADRA2B, the gene encoding subtype B of the α2-adrenergic receptor, which influences norepinephrine activity. We examined in 207 participants whether variations in this gene are responsible for individual differences in affective influences on initial encoding that alter perceptual awareness. We examined the attentional blink, an attentional impairment during rapid serial visual presentation, for negatively arousing, positively arousing, and neutral target words. Overall, the attentional blink was reduced for emotional targets for ADRA2B-deletion carriers and noncarriers alike, which reveals emotional sparing (i.e., reduction of the attentional impairment for words that are emotionally significant). However, deletion carriers demonstrated a further, more pronounced emotional sparing for negative targets. This finding demonstrates a contribution of genetics to individual differences in the emotional subjectivity of perception, which in turn may be linked to biases in later memory.

The effect of an NgR1 antagonist on the neuroprotection of cortical axons after cortical infarction in rats.

We investigated the effect of the soluble Nogo66 receptor (sNgR-Fc) on the protection of cortical axons after cortical infarction in rats. The cortical infarction was induced by photothrombotic cortical injury (PCI) in Sprague-Dawley rats, after which sNgR-Fc was injected into the lateral ventricle. The ipsilesional cortices were harvested for analyses using histochemical and transmission-electron microscope techniques. The involved signaling pathways, which include RhoA, JNK, c-JUN and ATF-2, were detected by Western blot. Serious pathologies were found in the brains of the rats after injury, including edemas in the axoplasms of axons that have no medulla sheath and a thickening or shrinkage in the sheath of the axons that have medulla sheathes. However, these pathologies improved after sNgR-Fc treatment. The levels of GTP-RhoA, p-JNK, p-c-JUN and p-ATF-2 in the PCI group were increased when compared with their levels in the sham-operation group (P < 0.05), and animals receiving the sNgR-Fc treatment showed lower expression levels of these proteins when compared with the sham-operation group (P < 0.05). Our results suggest that sNgR-Fc can alleviate the pathological changes of axons following cortical infarction via decreasing the activation of RhoA/JNK signaling pathways.

A clearing in the objectivity of aesthetics?

As subjective experiences go, beauty matters. Although aesthetics has long been a topic of study, research in this area has not resulted in a level of interest and progress commensurate with its import. Here, we briefly discuss two recent advances, one computational and one neuroscientific, and their pertinence to aesthetic processing. First, we hypothesize that deep neural networks provide the capacity to model representations essential to aesthetic experiences. Second, we highlight the principal gradient as an axis of information processing that is potentially key to examining where and how aesthetic processing takes place in the brain. In concert with established neuroimaging tools, we suggest that these advances may cultivate a new frontier in the understanding of our aesthetic experiences.

Expressing fear enhances sensory acquisition.

It has been proposed that facial expression production originates in sensory regulation. Here we demonstrate that facial expressions of fear are configured to enhance sensory acquisition. A statistical model of expression appearance revealed that fear and disgust expressions have opposite shape and surface reflectance features. We hypothesized that this reflects a fundamental antagonism serving to augment versus diminish sensory exposure. In keeping with this hypothesis, when subjects posed expressions of fear, they had a subjectively larger visual field, faster eye movements during target localization and an increase in nasal volume and air velocity during inspiration. The opposite pattern was found for disgust. Fear may therefore work to enhance perception, whereas disgust dampens it. These convergent results provide support for the Darwinian hypothesis that facial expressions are not arbitrary configurations for social communication, but rather, expressions may have originated in altering the sensory interface with the physical world.

Soluble NgR fusion protein modulates the proliferation of neural progenitor cells via the Notch pathway.

NogoA, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein are CNS myelin molecules that bind to the neuronal Nogo-66 receptor (NgR) and inhibit axon growth. The NgR antagonist, soluble NgR1-Fc protein (sNgR-Fc), facilitates axon regeneration by neutralizing the inhibitory effects of myelin proteins in experimental models of CNS injury. Here we aim to investigate the effect of sNgR-Fc on the proliferation of neural progenitor cells (NPCs). The hippocampus cells of embryonic rats were isolated and cultured in vitro. The expression of nestin, ßIII-Tubulin, GFAP and Nogo-A on these cells was observed using immunocytochemistry. In order to investigate the effect on proliferation of NPCs, sNgR-Fc, MAG-Fc chimera and Notch1 blocker were added respectively. The total cell number for the proliferated NPCs was counted. BrdU was applied and the rate of proliferating cells was examined. The level of Notch1 was analyzed using Western blotting. We identified that NogoA is expressed in NPCs. sNgR-Fc significantly enhanced the proliferation of NPCs in vitro as indicated by BrdU labeling and total cell count. This proliferation effect was abolished by the administration of MAG suggesting specificity. In addition, we demonstrate that sNgR-Fc is a potent activator for Notch1 and Notch1 antagonist reversed the effect of sNgR-Fc on NPC proliferation. Our results suggest that sNgR-Fc may modulate Nogo activity to induce NPC proliferation via the Notch pathway.

Erector Spinae Plane Block in the Emergency Department for Upper Extremity: A Case Report.

INTRODUCTION: The erector spinae plane block (ESPB) has been described as an effective analgesic modality in the emergency department (ED) for thoracic pain. It has not previously been described to treat ED patients with pain in the upper extremity. CASE REPORT: We present a case of a 52-year-old female who presented to the ED with an acute exacerbation of her chronic radicular left arm pain originating after a fall she sustained one year prior. After a variety of analgesic modalities failed to control her pain, an ESPB was used to successfully treat her pain and facilitate discharge from the ED. CONCLUSION: A significant portion of patients who present to the ED have underlying chronic pain; however, opioids are a potentially dangerous and ineffective modality to treat chronic pain. In addition to avoiding opiates, the ESPB has the advantage of preserving motor function, thus avoiding the complications associated with brachial plexus blockade.

Blockade of Nogo receptor ligands promotes functional regeneration of sensory axons after dorsal root crush.

A major impediment for regeneration of axons within the CNS is the presence of multiple inhibitory factors associated with myelin. Three of these factors bind to the Nogo receptor, NgR, which is expressed on axons. Administration of exogenous blockers of NgR or NgR ligands promotes the regeneration of descending axonal projections after spinal cord hemisection. A more detailed analysis of CNS regeneration can be made by examining the growth of specific classes of sensory axons into the spinal cord after dorsal root crush injury. In this study, we assessed whether administration of a soluble peptide fragment of the NgR (sNgR) that binds to and blocks all three NgR ligands can promote regeneration after brachial dorsal root crush in adult rats. Intraventricular infusion of sNgR for 1 month results in extensive regrowth of myelinated sensory axons into the white and gray matter of the dorsal spinal cord, but unmyelinated sensory afferents do not regenerate. In concert with the anatomical growth of sensory axons into the cord, there is a gradual restoration of synaptic function in the denervated region, as revealed by extracellular microelectrode recordings from the spinal gray matter in response to stimulation of peripheral nerves. These positive synaptic responses are correlated with substantial improvements in use of the forelimb, as assessed by paw preference, paw withdrawal to tactile stimuli and the ability to grasp. These results suggest that sNgR may be a potential therapy for restoring sensory function after injuries to sensory roots.

Resolution of disulfide heterogeneity in Nogo receptor I fusion proteins by molecular engineering.

NgRI (Nogo-66 receptor) is part of a signalling complex that inhibits axon regeneration in the central nervous system. Truncated soluble versions of NgRI have been used successfully to promote axon regeneration in animal models of spinal-cord injury, raising interest in this protein as a potential therapeutic target. The LRR (leucine-rich repeat) regions in NgRI are flanked by N- and C-terminal disulfide-containing 'cap' domains (LRRNT and LRRCT respectively). In the present work we show that, although functionally active, the NgRI(310)-Fc fusion protein contains mislinked and heterogeneous disulfide patterns in the LRRCT domain, and we report the generation of a series of variant molecules specifically designed to prevent this heterogeneity. Using these variants we explored the effects of modifying the NgRI truncation site or the spacing between the NgRI and Fc domains, or replacing cysteines within the NgRI or IgG hinge regions. One variant, which incorporates replacements of Cys²66 and Cys³°9 with alanine residues, completely eliminated disulfide scrambling while maintaining functional in vitro and in vivo efficacy. This modified NgRI-Fc molecule represents a significantly improved candidate for further pharmaceutical development, and may serve as a useful model for the optimization of other IgG fusion proteins made from LRR proteins.

Modified insertion technique for a sustained-release dexamethasone intravitreal implant (Ozurdex®).

PURPOSE: We describe a modified injection technique that adheres a sustained-release dexamethasone intravitreal implant (Ozurdex®) to the vitreous base. OBSERVATIONS: This modified technique was applied after removal of a prior dislocated Ozurdex® that migrated into the anterior chamber in one patient, and also on another patient bothered by perception of a large floater induced by a free-floating Ozurdex® in the vitreous cavity previously inserted with the conventional technique. The main feature of this new technique consisted of altering the conventional "bevel-up" orientation of the insertion needle tip towards the vitreous cavity to the modified "bevel-down" orientation of the needle tip directed towards the pars plana and vitreous base, for the purpose of adhering a portion of or the entire dexamethasone implant to the vitreous base. Neither patient developed postoperative complications with this technique. CONCLUSIONS AND IMPORTANCE: This modified insertion technique allows adherence of Ozurdex® to the vitreous base and avoids adverse effects associated with a free-floating Ozurdex®, such as its migration into the anterior chamber, or visual disturbance associated with movement of the implant.

Synaptic degeneration of retinal ganglion cells in a rat ocular hypertension glaucoma model.

AIMS: Glaucoma is a common neurodegenerative disease that affects retinal ganglion cells (RGCs) and their axons. Little is known of the synaptic degeneration involved in the pathophysiology of glaucoma. Here we used an experimental ocular hypertension model in rats to investigate this issue. METHODS: Elevated intraocular pressure (IOP) was induced by laser coagulation of the episcleral and limbal veins. RGCs were retrogradely labeled with Fluoro-Gold (FG). The c-fos protein was used as a neuronal connectivity marker. Expression of c-fos in the retinas was investigated by immunohistochemistry at 5 days and 2 weeks after the induction of ocular hypertension. Both surviving RGCs as revealed by retrograde FG-labeled and c-fos-labeled RGCs were counted. RESULTS: The c-fos protein was mainly expressed in the nuclei and nucleoli of cells in the ganglion cell layer and inner nuclear layer in the normal retina. We also confirmed that c-fos was also expressed in the nuclei and nucleoli of RGCs retrogradely labeled with FG. There was no significant RGC loss at 5 days but about 13% RGC loss at 2 weeks after the induction of ocular hypertension. The number of RGCs expressing c-fos was significantly lower in the experimental animals at both 5 days and 2 weeks than normal. CONCLUSION: Our study suggests that there is synaptic disconnection for RGCs after ocular hypertension and it may precede the cell death in the early stage. It may provide insight into novel therapeutic strategies to slow the progress of glaucoma.